Plants and microorganisms may be modified to produce bioactive compounds of medical interest. When the plant or microorganism is edible, it is potentially both the site of synthesis and the vehicle for delivering the bioactive compound. Such a synthesis-delivery system can be relatively inexpensive and free of the pathogens that may be associated with the cultured animal cells used in conventional vaccine and therapeutic compound production methods. Plant and non-plant systems that have been proposed for either vaccine or therapeutic compound production or such production and delivery include:
1) Plants whose genetic material has been transformed; PA1 2) Plants infected with genetically modified plant viruses; PA1 3) Genetically altered and attenuated pathogenic microorganisms; and PA1 4) Genetically altered commensal microorganisms.
To be of value, however, the modified plant or microorganism must be capable of synthesizing the vaccine or therapeutic compound of interest in quantities sufficient to generate a meaningful biological response. Additionally, the vaccine or therapeutic compound, if administered by the oral route, must not be degraded in the digestive tract of the treated animal subject. However, only genetically altered microbial mammalian pathogens have been shown to induce an immune response or effective immune protection against a mucosal pathogen.
Microorganisms have a potential advantage as a medically useful compound delivery vehicle, as compared to genetically transformed or virus-infected plants, in that microorganisms have a well characterized, malleable genetic system for synthesis of the bioactive compound. As a result, genetic manipulation of the microorganism is more readily accomplished than that of the plant. On the other hand, attenuated pathogenic microorganisms engineered to deliver medically useful compounds carry a constant risk of reversion or transformation to the virulent state; even the perception of that risk is a hindrance to the commercial use of such systems. Similarly, genetic manipulation of commensal microorganisms, which by definition already have the ability to survive in their human or other animal host, carries the risk that the ability to live symbiotically with the host may be destroyed and, furthermore, growth or other properties detrimental to the host may be acquired.
The present invention utilizes plants infected with genetically modified endophytic microorganisms as the vehicle for therapeutic or prophylactic compound synthesis and delivery. In some embodiments of the invention, the microorganism is propagated inside a plant, so that the plant becomes the delivery vehicle for the genetically modified microorganism and the compound. Until the present invention, plants had been infected with genetically modified endophytic microorganisms only for purposes of synthesizing pesticides in the plant, thereby eliminating the need for spraying the plant with conventional organic chemical or biological pesticides potentially harmful to humans and animals.